Intraperitoneal Dedifferentiated Liposarcoma: Unveiling a Rare Diagnosis in Peritoneal Fluid Cytology – A Case Report with Literature Review Open Access

Sarcomas are rarely diagnosed on effusion cytology, with the reported literature limited to case reports and infrequent case series. It requires a high level of suspicion, coupled with thorough consideration of clinical and radiological findings, as cells often lose their characteristic morphology and tend to appear more rounded and epithelioid in effusion cytology specimens, potentially leading to a misdiagnosis of mesothelioma or metastatic adenocarcinoma. Here, we present a case of a 70-year-old male with a large intraperitoneal mass with a prior biopsy history of spindle cell neoplasm. Peritoneal fluid cytology revealed singly scattered clusters of large pleomorphic cells with an epithelioid morphology. With the aid of cell block and immunohistochemistry (IHC), a diagnosis of dedifferentiated liposarcomas was suggested, which was later confirmed on resection specimen.

A 70-year-old male patient presented to the Surgery Outpatient Department (OPD) with a 2-month history of abdominal distension and pain. Contrast-enhanced computed tomography of the abdomen revealed an intraperitoneal mass measuring 17 × 13 cm, located in the mid-abdomen and extending into left lumbar region. The lesion extended posteriorly, encasing the 3rd part of the duodenum, abutting the abdominal aorta, and further extending into the left lumbar region. A trucut biopsy was performed, and histopathological examination revealed a spindle cell neoplasm. IHC staining showed positivity for smooth muscle actin (SMA), patchy positivity for S100, and positivity for desmin. However, CD34, ALK, and CD117 markers were negative. Based on these findings, a diagnosis of low-grade myofibroblastic/smooth muscle neoplasm was rendered. Further IHC analysis was not conducted because of the limited tissue available for additional markers.

Peritoneal fluid obtained from the patient revealed a mixture of benign and reactive mesothelial cells along with atypical cells displaying epithelioid morphology, characterized by coarse nuclear chromatin, prominent nucleoli, and abundant cytoplasm. Cells showing binucleation and multinucleation were also observed (Fig. 1). No spindle cells were seen. IHC performed on the cell block demonstrated positivity for SMA, while calretinin was negative, confirming atypical nature of the cells and possible diagnosis of leiomyosarcoma. However, subsequent MDM2 IHC showed diffuse nuclear positivity in the atypical cells, implying a diagnosis of dedifferentiated liposarcoma. Cytology was reported as positive for malignancy, suggestive of metastatic deposits of dedifferentiated liposarcoma (Fig. 2).

Subsequently, we received the resection specimen consisting of a large intraperitoneal mass measuring 18 × 17 cm with adhered intestinal loops. Histopathological examination of the specimen revealed a predominantly low-grade, spindle cell neoplasm. However, there were also areas within the tumor exhibiting high-grade features, characterized by cells with epithelioid morphology, enlarged nuclei, multinucleation consistent with findings from cytological evaluation (Fig. 3). Retained H3K27me3 expression ruled out malignant peripheral nerve sheath tumor, and negativity for myogenin and myoD1 helped to exclude rhabdomyoblastic differentiation. IHC for MDM2 and p16 was diffusely positive, confirming the diagnosis of dedifferentiated liposarcoma. Postoperative period was uneventful. The patient has been on regular follow-up for the past 6 months and has reported no specific complaints or evidence of relapse.

The diagnosis of sarcoma on effusion cytology typically occurs within the context of a known primary tumor. Subtyping them on fluid samples presents challenges due to their tendency to assume rounded shape, cytoplasmic vacuolations, or cohesiveness, potentially leading to variations in appearance compared to histopathological findings. Besides, typically the high-grade cells are detected in fluid, making them easily recognizable as malignant cells but pose diagnostic challenge due to striking resemblance to malignant mesothelial/adenocarcinoma cells.

Sarcomas comprise a minority of malignant effusions, accounting for less than 6% of reported cases [1, 2]. Owing to the rarity of sarcomas manifesting in effusion cytology, literature search on this specific scenario showed only few documented case series and isolated case reports. In pediatric populations, the embryonal rhabdomyosarcomas, osteosarcoma, and Ewing sarcoma are the most frequently encountered sarcomas in fluid specimens. On the other hand, in adults, angiosarcoma, pleomorphic liposarcoma, leiomyosarcoma are more common [3‒5]. Geisinger et al. [6] described the presence of pleomorphic giant cells with cytoplasmic vacuolations as a diagnostic feature of pleomorphic liposarcoma. A high index of suspicion and clinicoradiological information are essential as cytology can be deceptive [1]. However, in recent times, with the aid of IHC on cell block with molecular analysis, a cytological diagnosis is achievable. In a study conducted by Ng JKM et al. [7] focusing on 6 patients with liposarcoma, 3 patients exhibited dedifferentiation on histology. Effusion cytology revealed high-grade tumor cells in two of these patients. Immunoreactivity for CDK4 and MDM2 on cell blocks was observed in all 3 patients. They concluded that with adequate cellularity for immunocytochemistry and molecular testing, a diagnosis of liposarcoma can be rendered on fluid samples. Abadi et al. [2] in their study outline the cytological observations such as single-cell arrangement, indistinct cell borders, nuclear pleomorphism, multinucleation in sarcomatous pleural effusion. Similar findings were observed in our case. Categorizing the lesion as liposarcoma on fluid cytology sample based on morphological findings alone was challenging. However, leveraging clinicoradiological findings, along with a biopsy suggestive of spindle cell neoplasm and subsequent cell block with additional IHC markers, enabled us to reach a diagnosis. Dagli et al. [8] reported a case of pleural liposarcoma in which pleural cytology revealed tumor cells forming complex papillary structures with fibrovascular core. Additionally, immunocytochemistry indicated positivity for CA125. They concluded that these findings suggest a possibility of metastatic ovarian origin. However, subsequent biopsy identified the lesion as liposarcoma of a myxoid type. In a retrospective study conducted by Sharma et al. [9] spanning a 20-year period at their institution, among 57 cases of sarcomatous effusion, only 3 cases were attributed to dedifferentiated liposarcoma, highlighting its rarity in serous effusions. Notably, 1 case of retroperitoneal dedifferentiated liposarcoma was misdiagnosed as adenocarcinoma. The study also highlights that fluid positive for sarcoma cells portends poor prognosis for the patient. The various cytological features observed on effusion cytology of 14 cases of liposarcoma described in the literature have been summarized and compared with the features we observed in our case (Table 1).

The cytological diagnosis of dedifferentiated liposarcoma is arduous and requires a high level of suspicion. Clinicoradiological correlation is of utmost importance in this regard. Sarcoma cells exhibit altered morphology in fluid specimens, typically representing high-grade areas and may mimic carcinoma/mesothelioma. Spindle cells may not be observed in fluid cytology samples. Dyscohesive cell clusters, single atypical cells, multinucleation, and the absence of 3-dimensional cell balls/papillae could serve as pointers for considering sarcoma in effusion cytology. IHC on cell block samples aids in accurate diagnosis, guiding appropriate patient management.

Ethical approval was not required for this study in accordance with local/national guidelines. Written informed consent has been taken by the patient for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

S.P., V.M., and N.S. were responsible for the reporting and diagnosis of the case. S.P. and V.M. contributed for the drafting of the manuscript. N.K. and V.M.G. were responsible for manuscript review and editing. All the authors read and approved the final manuscript.

All data generated during this study have been included in the article. Further inquiries can be directed to the corresponding author.